Une méta-analyse en réseau (NMA ; Ismaila A.S. et al, Adv Ther 2022;39(11):4961–5010) a comparé l'efficacité de l'UMEC/VI par rapport à l'IND/GLY chez les patients symptomatiques atteints de BPCO. L'objectif de cette étude était d'évaluer le rapport coût–efficacité de l'UMEC/VI 62,5/25 μg une fois par jour par rapport à l'IND/GLY 110/50 μg une fois par jour pour le traitement de la BPCO, du point de vue du système national de soins de santé (NHS) du Royaume-Uni. Un modèle validé d'équation de risque liée (GALAXY ; Briggs A. H. et al, Med Decis Making 2017;37:4) qui prédit la progression de la maladie BPCO, les coûts des soins de santé, les années de vie (LY) et les années de vie pondérées par la qualité (QALY) a été utilisé. Les caractéristiques à la Baseline ont été dérivées d'un essai clinique mené chez des patients éligibles à la bithérapie (NCT02799784). Les effets du traitement ont été dérivés d'une AMN et comprenaient un changement par rapport aux valeurs initiales du VEMS1, du SGRQ et une réduction des exacerbations. Au niveau de l'horizon de vie, UMEC/VI a fourni 0,307 LY et 0,036 QALY supplémentaires, avec des économies de coûts de 1948 £ par rapport à IND/GLY. Les résultats étaient en faveur de UMEC/VI par rapport à l'IND/GLY dans la majorité des scénarios et des analyses de sensibilité (les exceptions comprennent des horizons temporels plus courts, un intervalle de confiance supérieur pour le SGRQ et les effets du traitement des exacerbations) (Tableau 1). Dans le contexte des services de santé nationaux britannique, le traitement par UMEC/VI devrait améliorer les résultats de santé et réduire les coûts par rapport à l'IND/GLY chez les patients atteints de BPCO symptomatique.

To assess the health economic evidence of chronic heart failure (CHF) treatments through a targeted literature review.

To evaluate the cost-effectiveness of once-daily fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/25 μg compared with once-daily tiotropium (TIO) 18 μg in patients with symptomatic chronic obstructive pulmonary disease (COPD) and a history of exacerbations from a United Kingdom (UK) National Healthcare System (NHS) perspective. The GALAXY linked risk equation COPD disease model (Briggs AH et al., 2017 Med Decis Making; 37:4) was used to predict healthcare costs, life-years (LYs), quality adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICER) over a lifetime horizon. The model was populated with baseline characteristics and treatment effects, including change from baseline in FEV1 and St George’s Respiratory Questionnaire score, from a 12-week randomized, double-blind trial comparing FF/UMEC/VI and TIO in symptomatic COPD patients with a history of exacerbations (NCT03474081). Healthcare resource use, drug costs and unit costs (£, 2021) were from UK public sources and published literature. Costs and health outcomes (except LYs) were discounted at 3.5% per year. Treatment with FF/UMEC/VI, compared with TIO, was predicted to result in fewer exacerbations per patient per year (1.188 vs 1.254), and greater total LYs (9.229 vs 8.836) and QALYs (5.127 vs 4.684) at a lower total cost (£13,710 vs £14,590). FF/UMEC/VI was therefore the dominant treatment. Across sensitivity and scenario analyses, FF/UMEC/VI remained dominant or had an ICER below £10,000 per QALY. In probabilistic sensitivity analysis, the probability of FF/UMEC/VI being cost-effective versus TIO was 100% at a willingness-to-pay threshold of £20,000 per QALY. In a UK NHS setting, treatment with FF/UMEC/VI was predicted to improve health outcomes and be highly cost-effective versus TIO in patients with symptomatic COPD and a history of exacerbations.

we aim to examine how those involved in modelling and commissioning BDVIE understand the use of evidence from mathematical models in informing resource allocation decisions at a global level.Methods: Fourteen semi-structured interviews were conducted with mathematical modelers (evidence producers) and seniorlevel employees at international organizations (evidence consumers) at a global level.Information was collected on stakeholders' experiences and perceptions of the use of mathematical models at global level.Mathematical modelers were purposively sampled by their extensive vaccine modelling experience at a global level.Data from interviews were mapped to Langley's framework, which acknowledges the spectrum of evidence use typologies in organizations.PRE-LIMINARY Results: BDVIE are used concurrently for different purposes.We found that this type of evidence serves for accountability and advocacy purposes to solicit funding from partner organizations.Research that does not create a compelling case in line with decision-makers' expectations, is less likely to be regarded as useful.In this context, evidence is not commissioned to solve problems or to support innovative science.Evidence use is strongly influenced by social interactions among evidence producers and consumers.Conclusions: This research suggests that commissioned evidence is mainly used symbolically for advocacy purposes by agencies that provide donor assistance for health.Rather than leading resource allocation decisions, research evidence is commissioned to justify global actors' pursuit in the complex policy-making venue around vaccines.We conclude that there is a lack of transparency on resource allocation decision-criteria and their weighting.To what extent research evidence is explicitly used in resource allocation decisions at global level remains unclear.

This systematic literature review highlights the economic burden of hospitalized adults with COVID-19 in Europe and Asia. We searched MEDLINE, EMBASE, and EconLit from December 1, 2019 to October 26, 2020. Two independent reviewers assessed all abstracts according to the eligibility criteria. Studies with queries were referred to a third reviewer to reach agreement. Studies that met the inclusion criteria after full-text review were extracted and critically appraised. After removing duplicates, 845 citations were identified through database searches. Sixty-three citations were included for full-text screening; seven observational studies were included (three from Asia, four from Europe). Six studies reported baseline characteristics for hospitalized patients, and all studies reported comorbidities. Commonly reported comorbidities included diabetes (range 11.2%-50%) and hypertension (range 16.3%-64%). The proportion of patients requiring ventilation ranged from 2% to 89%. One study reported that all patients needed invasive ventilation, but due to lack of ventilators, only 64.7% received it. Pharmacology therapy use was reported in five studies: one study treated all patients with hydroxychloroquine+azithromycin, another reported propofol and cisatracurium as the most frequently used therapies. Use of antibiotics ranged from 31% to 100%, and antivirals ranged from 40% to 98.6%. Length of hospital stay was reported in five studies and varied greatly, from mean 4.6 days (SD 2.1) to median 16 days (IQR 10-23). One study estimated per-patient costs for COVID-19 patients at $4,552 for mild cases, $11,058 for severe cases, and $16,652 for critically ill cases. Research showed that the economic burden of COVID-19 hospitalized patients in Europe and Asia is high. This literature is growing, as our search strategy found 800 new citations published from October 2020 to January 2021. These results may be useful for future studies seeking to increase the information base on the economic burden of hospitalized COVID-19 patients.

This systematic literature review highlights the economic burden of hospitalized adults with COVID-19 in the USA. We searched MEDLINE, EMBASE, and EconLit from December 1, 2019 to October 26, 2020. All abstracts were reviewed according to the eligibility criteria, by two systematic reviewers independently. Studies with queries were referred to a third reviewer to reach agreement. Studies that met the inclusion criteria after review of full-text were extracted and critically appraised. After removing duplicates, 845 citations were identified through database searches. A total of 45 citations were included for full-text screening; 9 observational studies were included (8 cohort studies and 1 case series). Patient age ranged from a mean of 50-69.2 years, and the proportion of males in all patients ranged from 50.5% to 61.9%. Mean length of stay (LOS) ranged from 1.4 days (SD 4.3) to 8.9 days. Black patients had a median LOS of 6 days compared to white patients of 7 days. One study reported mean LOS in the intensive care unit (ICU) of 15.5 days (range 3-46). The proportion of patients moved to the ICU ranged from 4% to 35.7%. The proportion of non-invasive ventilation ranged from 0.8% to 8.5% and the proportion of invasive ventilation ranged from 0% to 78.2%. Pharmacology therapy was well reported; treatments used in more than one study included: antibiotics, steroids, hydroxychloroquine, remdesivir, and tocilizumab. None of the included studies reported direct/indirect costs, nor data for productivity loss. Research on the economic burden of COVID-19 in the USA is limited regarding resource utilization; we found no studies that focused on the cost burden associated with COVID-19. These results may be useful for future studies seeking to increase the information base on the economic burden of COVID-19 in the hospital setting.

The 24-week EMAX trial in symptomatic patients with chronic obstructive pulmonary disease (COPD) and low exacerbation risk not receiving inhaled corticosteroids demonstrated clinical benefits of once-daily umeclidinium/vilanterol (UMEC/VI) 62.5/25 mcg versus once-daily UMEC 62.5 mcg and twice-daily salmeterol (SAL) 50 mcg. This post hoc analysis assessed cost-effectiveness of UMEC/VI versus UMEC or SAL from a UK payer perspective in patients with COPD and no exacerbation history in the EMAX trial. The validated GALAXY risk equation model was populated with EMAX patient characteristics, treatment effects, rescue medication use data, and 2020 UK costs. Treatment effects included forced expiratory volume in 1 second (FEV1) and St George’s Respiratory Questionnaire (SGRQ); no treatment effect was included for exacerbations. Model outputs included estimated exacerbation rates, survival, costs, life years (LYs), and quality-adjusted LYs (QALYs); incremental cost-effectiveness ratio (ICER) was calculated for cost per QALY gained. The base case used a 10-year time horizon, excluded treatment discontinuation, and discounted future costs and QALYs by 3.5% annually. Sensitivity and scenario analyses assessed robustness of model results. Despite greater incremental drug costs, UMEC/VI was the dominant treatment versus UMEC and SAL, providing an additional 0.090 LYs (95% CI: 0.035, 0.158) and 0.055 QALYs (-0.059, 0.168) with cost savings of £690 (-£1306, -£231) versus UMEC, and 0.174 LYs (0.076, 0.286) and 0.204 QALYs (0.079, 0.326) with cost savings of £1336 (-£2032, -£1006) versus SAL. In scenario and sensitivity analyses, ICERs for UMEC/VI versus UMEC were sensitive to time horizon (5 years: ICER=£4) and SGRQ treatment effect (upper CI: ICER=£12,337), while UMEC/VI was consistently dominant versus SAL. Based on model predictions from a UK NHS perspective, symptomatic patients with COPD and no exacerbation history receiving UMEC/VI are expected to have better outcomes (QALYs and survival) at lower costs versus UMEC and SAL. FUNDING: GSK (study 209845; EMAX study 201749/NCT03034915).

Oncologic/hematologic economic evaluations require estimation of mean survival benefit, which requires extrapolation of survival beyond the observed clinical trial data. In this analysis the impact of restricted data availability (i.e. small sample sizes and short follow-up) on parametric estimates of survival was compared between three cancer populations with differing prognosis (chronic myeloid leukemia (CML), stage IV lung cancer and stage IV prostate cancer). Data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) registry were employed. Lung and prostate cancer patients diagnosed between 1998-2003 and CML patients diagnosed from 1988-1998, with follow-up data available until 2016 were included. Overall survival was estimated using standard parametric models (exponential, Weibull, log-logistic, log-normal, and Gompertz). For each population, survival analyses were run for 4 sample sizes (n= 50, 100, 250, 500) and 5 follow-up durations (follow-up months = 12, 24, 60, 120, 240) yielding 20 permuted scenarios. Using bootstrap techniques, mean survival estimates and root mean square error (RMSE) relative to the observed mean survival for the whole SEER sample were calculated for each scenario in each population. Mean overall survival was 7.08, 7, and 0.08 years for patients with CML, prostate, and lung cancer, respectively. Across the populations, exponential and Weibull distributions were relatively robust to data limitations. Log-logistic and log-normal distributions were sensitive (large RMSE) to small sample sizes. Gompertz distributions produced the largest overestimates and RMSE across the scenarios. RMSE was higher in populations with a better prognosis (CML and prostate), especially for the restricted follow-up time scenarios. This analysis showed that log-normal and log-logistic distributions are more sensitive to sample size restrictions and that restricted follow-up times have the biggest impact in populations with a better prognosis. Results highlight the importance of exercising caution in survival model selection.

A budget impact model was developed to assess the financial impact of introducing single inhaler, once-daily fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100μg/62.5μg/25μg to the UK National Health Service formulary for treatment of patients with moderate to severe COPD. Relevant inhaled corticosteroids (ICS)/ long-acting beta agonist (LABA) and LABA/ long-acting muscarinic antagonist (LAMA) fixed-dose combinations as well as ICS/LABA + LAMA multiple inhaler triple therapies (MITTs), approved for the treatment of COPD in the UK, were considered in the analysis. An epidemiological approach leveraging local prescribing data was used with a three-year time horizon. Only drug acquisition costs (in 2017 GBP) were considered. Model outputs included the number of COPD patients treated and incremental budget impact following the introduction of FF/UMEC/VI. In the base-case, it was assumed that market share of FF/UMEC/VI would be 2%, 7% and 10% in years 1-3, respectively, 100% of which was taken from ICS/LABA + LAMA MITTs and 100% patient compliance. Sensitivity analyses were performed on input parameters. Based on a conservative prevalence estimate, the number of COPD patients in the UK was 632,443, 636,573 and 640,711 in years one, two and three, respectively; with an estimated 12,649, 44,560 and 64,071 patients treated with FF/UMEC/VI. Introduction of FF/UMEC/VI to the formulary, with all market displacement coming from MITTs, would result in a cost-savings of £1,865,476, £6,571,810 and £9,449,323 in years one, two and three, respectively; resulting in the cumulative cost savings of £17,886,609. Results of one-way sensitivity analyses showed that the budget impact was most sensitive to cost (±10%) and uptake rates of FF/UMEC/VI (50% to 200%), with cost-savings over three-years ranging from £8,943,305 to £35,773,218. FF/UMEC/VI has potential to reduce costs for treatment of COPD patients in the UK, if FF/UMEC/VI were to displace market share from ICS/LABA + LAMA MITTs. Funding: GSK (HO1613835)

Introduction and objective Exacerbations associated with chronic obstructive pulmonary disease (COPD) are costly and affect health related quality of life (HRQoL) for patients. An economic model was developed to estimate the cost-effectiveness of once-daily single-inhaler triple-therapy, fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) Trelegy®, 100 µg/62.5 µg/22 µg and dual therapy, umeclidinium/vilanterol (UMEC/VI) Anoro®, 55 µg/22 µg from a UK NHS perspective using results from the IMPACT study (NCT02164513). Patients and methods The model combines a decision tree for the within-trial period (52 weeks) and a Markov model to predict lifetime costs and outcomes of FF/UMEC/VI compared with UMEC/VI. Risk equations for prediction of exacerbations (by severity of COPD) and FEV1 decline (based on exacerbation history) were derived using data from the TORCH study (NCT00268216). Baseline characteristics, efficacy and medication use were based on data from IMPACT. Direct costs, including drug acquisition costs were calculated using UK NHS reference costs and drug prices. Healthcare resource utilisation was based on published sources. Costs (2018 £) and health outcomes were discounted at 3.5% and modelled on a lifetime horizon. Sensitivity analyses were performed to evaluate the robustness of the model to variations in the underlying input parameters and assumptions. Results Patients treated with FF/UMEC/VI had fewer moderate and severe exacerbations, more life years gained, improved HRQoL and higher total costs compared with patients treated with UMEC/VI based on deterministic analyses (table 1). The incremental cost-effectiveness ratio (ICER) was £7451 per QALY gained. Sensitivity analyses identified that results were most sensitive to drug acquisition cost, utilities associated with moderate COPD and severe COPD, mortality risk in very severe COPD, and exacerbation rates. The ICERs ranged from £1110 to £13 793 per QALY. Probabilistic sensitivity analysis indicated a 73% chance that FF/UMEC/VI is cost-effective versus UMEC/VI at a willingness to pay threshold of £20 000 per QALY. Funding GSK (study number HO-17–17596). ICON Health Economics received funding from GSK to conduct the study only.Abstract P249 Table 1 Total combined outcomes from within trial period and Markov model over lifetime horizon

As acknowledged by international GOLD and Canadian treatment recommendations, inhaled triple therapy may be appropriate for some patients with chronic obstructive pulmonary disease (COPD). The cost-effectiveness of fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) vs. FF/VI was thus assessed from a Quebec societal perspective, leveraging data from the IMPACT trial (NCT02164513). A validated linked risk equation, COPD disease progression, model (Briggs 2017 Med Decis Making 37:4) was populated with baseline characteristics, efficacy and medication use from IMPACT. Quebec healthcare resource and societal and drug costs were applied, with future costs and health outcomes discounted at 1.5% annually. The analysis was probabilistic, with a lifetime horizon. Outputs included exacerbation rates, costs (2017 CAD), life-years (LYs), quality-adjusted life years (QALYs) gained and incremental cost effectiveness ratio (ICER) per QALY. Sensitivity analyses explored the robustness of results by varying parameter values and assumptions. Compared with FF/VI, FF/UMEC/VI resulted in fewer moderate and severe exacerbations (10.52 and 3.38 versus 11.12 and 3.48), translating to fewer total per patient per year exacerbations (1.53 versus 1.62). Overall mean (95% CI) incremental costs were $2,489 ($1,861, $3,212) for FF/UMEC/VI compared with FF/VI but total indirect non-drug costs were lower ($4,428 versus $4,608). Incremental LYs (undiscounted, 95% CI) and QALYs were 0.14 (0.07, 0.21) and 0.13 (0.09, 0.18), resulted in an ICER of $18,887 ($14,625, $25,587) per QALY. The probability of FF/UMEC/VI being cost-effective compared with FF/VI was 100%, at a willingness-to-pay WTP) threshold of $50,000 per QALY. Across all scenarios considered the ICER ranged from $14,281 to $23,798, remaining below the WTP threshold. Results were most sensitive to time horizon, efficacy of treatment post-discontinuation and changing FF/VI cost. FF/UMEC/VI was predicted to improve health outcomes and to be a cost-effective option for treatment of patients with moderate/severe COPD and a history of exacerbations, compared with FF/VI in Quebec.

Results of the IMPACT trial have shown the clinical benefit of single inhaler, once-daily fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100μg/62.5μg/25μg compared to UMEC/VI (62.5/25μg) in patients with moderate/severe COPD, from a Canadian public health care perspective. The lifetime horizon analysis used a validated COPD disease progression model (Briggs et al., Med Decis Making 37;4 2017) populated with baseline inputs and treatment effects from the IMPACT trial (NCT02164513). Costs and health outcomes after year one were discounted at 1.5%. Sensitivity analyses explored the robustness of results to varying parameter values and assumptions. All analyses were probabilistic (5000 iterations) and outputs included exacerbation rates, costs (2018 CAD), life-years (LYs,) quality-adjusted life years (QALYs) gained and incremental cost effectiveness ratio (ICER) per QALY. For FF/UMEC/VI and UMEC/VI, per patient over their lifetime, the predicted cumulative number of exacerbations was 10.16 and 11.12, accumulated LYs (undiscounted) were 9.07 and 8.96, accumulated QALYs were 5.25 and 5.13,and total accumulated costs were $64,678 and $62,877 respectively . Patients who received FF/UMEC/VI gained an additional 0.12 LYs (95% CI 0.05 to 0.19), 0.12 QALYs (95% CI, 0.08 - 0.17) with an additional cost of $1,801 (95% CI $1,225- $2,316). The resulting ICER was $14,864 (95% CI, $11,151 - $20,850) per QALY gained. In all sensitivity analyses, FF/UMEC/VI remained cost-effective, including at shorter time horizons of 5 and 10 years. Treatment with FF/UMEC/VI was predicted to improve health outcomes and be a cost-effective option for treatment of moderate/severe COPD compared with UMEC/VI, in Canada.

Introduction and objectives The IMPACT trial (NCT02164513) showed superior exacerbation reduction and lung function improvement with once-daily single inhaler triple therapy, fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/22 µg, compared with once-daily FF/VI 100/22 µg, for patients with symptomatic COPD and a history of exacerbations. An economic model was developed to assess the cost-effectiveness of FF/UMEC/VI vs FF/VI from a UK NHS perspective, using results from IMPACT. Methods The model combined a decision-tree for the trial period, with longer-term outcomes extrapolated via a Markov model with health states reflecting COPD severity and exacerbation history. Disease progression and exacerbation rates were determined by risk equations based on the 3 year Towards a Revolution in COPD Health study (TORCH, NCT00268216). The model was populated with baseline characteristics, efficacy and medication use from IMPACT, while healthcare resource use and utility estimates came from the literature. Medication and healthcare resource use were costed using UK drug prices and unit costs (2018 £). Results are for a lifetime horizon with costs and health outcomes (except life-years) discounted at 3.5%. Results Treatment with FF/UMEC/VI, compared with FF/VI, resulted in fewer moderate and severe exacerbations (6.460 and 1.501 vs 6.686 and 1.528), more life-years (8.874 vs 8.577) increased quality-adjusted life years (QALYs, 6.565 vs 6.291) and higher total costs (£24 843 vs £23,549). Patients receiving FF/UMEC/VI gained an additional 0.275 QALYs for an additional cost of £1,294, compared to those receiving FF/VI, to give an incremental cost-effectiveness ratio (ICER) of £4712 per QALY gained. In deterministic sensitivity/scenario analyses, ICERs ranged from dominant to £7502 per QALY gained, with results most sensitive to drug acquisition costs, utility associated with moderate COPD, duration of treatment effect and time horizon. In probabilistic sensitivity analysis, the probability of FF/UMEC/VI being cost-effective vs FF/VI was 95% at a willingness-to-pay threshold of £20 000 per QALY. Conclusions Treatment with FF/UMEC/VI was predicted to improve health outcomes and to be a cost-effective option for patients with symptomatic COPD and a history of exacerbations, when compared with FF/VI, in the UK. Funding GSK (study number HO-17–17596). ICON Health Economics received funding from GSK to conduct the study only.